Laminated microfluidic structures and method for making

ABSTRACT

A method for making a polymeric microfluidic structure in which two or more components (layers) of the microfluidic structure are fixedly bonded or laminated with a weak solvent bonding agent, particularly acetonitrile or a mixture of acetonitrile and alcohol. In an aspect, acetonitrile can be used as a weak solvent bonding agent to enclose a microstructure fabricated in or on a non-elastomeric polymer such as polystyrene, polycarbonate, acrylic or other linear polymer to form a three-dimensional microfluidic network. The method involves the steps of wetting at least one of the opposing surfaces of the polymeric substrate components with the weak solvent bonding agent in a given, lower temperature range, adjacently contacting the opposing surfaces, and thermally activating the bonding agent at a higher temperature than the lower temperature range for a given period of time. The contacted polymeric substrates may also be aligned prior to thermal activation and compressed during thermal activation. A laminated, polymeric microfluidic structure is also disclosed.

BACKGROUND OF THE INVENTION

1. Field of the Invention

Embodiments of the invention generally pertain to the field ofmicrofluidics and, more particularly, to a laminated, polymericmicrofluidic structure and to a method for making a laminated, polymericmicrofluidic structure.

2. Description of Related Art

The technology of manipulating minute volumes of biological and chemicalfluids is widely referred to as microfluidics. The realized andpotential applications of microfluidics include disease diagnosis, lifescience research, biological and/or chemical sensor development, andothers appreciated by those skilled in the art.

A microfluidic structure including a substrate having one or moremicrofluidic channels or pathways and a cover plate or a second or moresubstrates with fluid pathways that may or may not be interconnected,may commonly be referred to as a microfluidic chip. Highly integratedmicrofluidic chips are sometimes called ‘labs on a chip’. Inorganicmicrofluidic chips having substrates made of glass, quartz or siliconhave advantageous organic solvent compatibilities, high thermal anddimensional stability and excellent feature accuracy. These chips aretypically fabricated using well-established microfabricationtechnologies developed for the semiconductor industry. However, thematerial and production costs of the inorganic chips may becomeprohibitively high especially when the fluidic pathway(s) requiressignificant area or the chip has to be disposable. In addition, manyestablished biological assays were developed utilizing the surfaceproperties of polymeric substrates. The research effort required toredevelop these assays on inorganic surfaces would require significanttime and resource investments.

As an alternative to inorganic microfluidic structures such as thosereferred to immediately above, microfluidic structures or devices canalso be made from polymeric materials. Polymeric microfluidic structureshave advantageous low material costs and the potential for massproduction. However, the fabrication of polymeric microfluidic chipspresents a variety of challenges. For example, microfluidic chips maycontain sealed microstructures. They can be formed by enclosing asubstrate having a pre-fabricated fluid pathway or other microfeatureswith a thin cover plate, or with one or more additional substrates toform a three-dimensional fluid network. The pathways or othermicrostructures have typical dimensions in the range of micrometers tomillimeters. This multilayer microfluidic structure is integrated, orjoined together, by various conventional techniques. These techniquesinclude thermal, ultrasonic and solvent bonding. Unfortunately, thesetechniques often significantly alter the mated surfaces and yielddistorted or completely blocked microfluidic pathways due, for example,to the low dimensional rigidity of polymeric materials under theaforementioned bonding conditions.

The use of adhesive lamination may circumvent some of these potentialdifficulties by avoiding the use of excessive thermal energy or a strongorganic solvent. However, the introduction of an adhesive layer to awall surface of an enclosed fluid pathway can cause other fabricationand/or application problems. Commercially available adhesives tend to beconforming materials with typical applied thicknesses of 12-100micrometers. The compressive force required to produce a uniform sealbetween component layers will often extrude the adhesive into the fluidpathways resulting in microchannel dimensional alteration orobstruction. An additional potential problem with using adhesives is theformation of an adhesive wall within the enclosed microstructure. Thepresence of this dissimilar material makes uniform surface modificationof the microstructure difficult. Furthermore, the manipulation orpatterning of an adhesive layer is difficult, limiting the use of theadhesives to uniform continuous sheets or layers between two opposingplaner surfaces. This restricts fluidic communication through a networkto one planer surface, as the fluid cannot flow through the adhesivelayer, preventing the use of a more versatile three-dimensional space.

The use of a strong organic solvent to join two or more discrete plasticparts is a well known practice in the art. In solvent welding, as thisprocess is referred to, lamination solvents work by aggressivelypenetrating the macromolecular matrix of the polymeric component. Thisloosens the macromolecule-to-macromolecule bonds, uncoiling or releasingthem from their polymer network to generate a softened surface. When twoopposing softened surfaces are brought into close proximity, newmacromolecular interactions are established. After the solventevaporates there is a newly formed macromolecular network at the bondedinterface with mechanical strength defined by the force of themacromolecular interaction. Exemplary strong organic solvents used forplastic lamination include ketones (acetone, methylethyl ketone or MEK),halogenated hydrocarbons (dichloromethane, chloroform,1,2-dichloroethane), ether (tetrahydrofurane or THF) or aromaticmolecules (xylene, toluene) and others known by those skilled in theart.

The use of the aforementioned strong solvents for bonding microfluidicchips with substrates composed of polystyrene, polycarbonate or acrylicis problematic. All of the solvents known to be used in the field ofsolvent bonding are “strong” (as defined by their ability to dissolvethe polymeric substrate) organic solvents. That is, these solvents tendto over-soften or dissolve the surface of the substrates during thebonding process. This may damage the microfluidic structure bycompletely erasing, blocking or destroying the fluid pathways when thesubstrates are laminated. Acetone, dichloromethane or xylene, forexample, begin to dissolve a polystyrene sheet within seconds ofapplication at room temperature. Although it is possible to weaken thesolvent strength by mixing the solvent with “inert” solvents such asmethanol or ethanol, the resulting bond often does not provide asatisfactory result.

The contemporary patent literature discloses using thermal bonding,thermal-melting adhesive, liquid curable adhesive, and elastomericadhesive approaches to enclose two opposing microfluidic structuresurfaces of the same or different materials. It is suggested that thesemethods are applicable to the fabrication of microchannels of variousshapes and dimensions. It is apparent, however, that these approachesrely on stringent control of the fabrication and process conditions,which may result in unacceptable fabrication throughput and productionyield.

Another reported technique suggests that the quality of a thermallylaminated polymeric microchannel can be drastically improved if theopposing substrates have different glass transition temperatures. Whilethis approach may provide a way to retain microstructural integrityduring thermal bonding, the success rate will rely on precise processcontrol. Consequently, its application to microfluidic chipmanufacturing is restricted.

A recent publication describes a method of creating a plurality ofrelief structures along the length of a microfluidic channel wall,projecting from the opposing surface in the non-functional area of thesubstrate. Subsequent deposition of a bonding material fills this reliefstructure, completing the bond. This method allegedly can increase themanufacturing yield of adhesive bonded microfluidic devices. Thesignificant challenge of dispensing the correct volume of bondingmaterial into the relief structures is not addressed. The necessarycontrol of the small volume of bonding material does not lend itself tohigh production yields.

In view of the foregoing, the inventors have recognized that a simple,reproducible, high yield method for enclosing polymeric microstructuresis needed. Such a method would be particularly valuable for thefabrication of microfluidic chips from polystyrene, which is the mostwidely used material for biochemical, cellular and biological assays,acrylics and polymeric materials. It would also be desirable to have amethod for microfluidic chip fabrication that is amenable to bothlaboratory use and manufacturing environments. Such a method wouldfurther be useful if it were applicable to the production of prototypedevices, as well as being substantially directly transferable tolarge-scale production. Microfluidic structures made according to theenvisioned methods would also be desirable for their economy and ease ofproduction. Accordingly, embodiments of the invention are directed tomicrofluidic structures and fabrication methods that address therecognized shortcomings of the current state of technology, and whichprovide further benefits and advantages as those persons skilled in theart will appreciate.

SUMMARY OF THE INVENTION

An embodiment of the invention is generally directed to a method formaking a polymeric microfluidic structure in which two or morecomponents (layers) of the microfluidic structure are fixedly bonded orlaminated with a weak organic solvent acting as a bonding agent. In aspecific aspect, the weak solvent bonding agent is acetonitrile (CH₃CN,CAS No. 75-05-8). According to an aspect of the embodiment, acetonitrilecan be used as a weak solvent bonding agent to enclose a microstructurefabricated in or on a non-elastomeric polymer such as polystyrene,polycarbonate, acrylic or other linear polymer to form athree-dimensional microfluidic network.

According to an aspect, the method involves the steps of wetting atleast one of the opposing surfaces of the polymeric substrate componentswith the weak solvent bonding agent in a given, lower temperature range,adjacently contacting the opposing surfaces, and thermally activatingthe bonding agent at a higher temperature than the lower temperaturerange for a given period of time. In an aspect, the lower temperaturerange is between about minus 10 to positive 35° C., and more usuallybetween about 0 to +20° C. The lower temperature range typicallyincludes what is referred to herein as room temperature. The highertemperature is above about +35° C. In an aspect, pressure is applied tothe adjacently contacted components to assist the laminating process. Itwill be appreciated that the higher temperature necessary for thermallyactivating the weak solvent bonding agent may depend on the laminationprocess and the applied pressure. The applied pressure may usually be upto about 10 psi. More particularly, the applied pressure may be up toabout 5 psi. In an aspect, an applied pressure range is up to about 2.5psi. Alternatively, the mass alone of the substrate may providesufficient bonding force, or a vacuum may be pulled that is sufficientto bring the surfaces into uniform contact. Illustrative compressiontime of the lamination process may range between about a few secondswhen a roll laminator is used, to about a few minutes when using aheated platen press, for example.

According to another aspect, the method is directed to producing amulti-layer microfluidic structure by repetitively applying a weaksolvent bonding agent to opposing surfaces of multiple (n) substratecomponents that may include one or more microstructures. In an aspect,the multiple substrate components can be slidingly aligned after theselected surfaces are wetted and opposing surfaces are in adjacentcontact, prior to thermally activating the bonding agent. According toanother aspect, the alignment can be carried out by vertically aligningand connecting discrete microstructures embedded at different substratelevels via vertically positioned through-holes in the substratecomponents.

According to another aspect, a polymeric, microstructural patternedsubstrate can be enclosed with a polymeric thin film bonded thereto witha weak solvent bonding agent that is thermally activated after the thinfilm is contacted with the substrate surface. According to this aspect,a contact surface of the substrate or the thin film can be wetted withthe weak solvent bonding agent prior to contact. Alternatively, thesurfaces can be adjacently contacted and the weak solvent bonding agentapplied to an exposed edge whence it is wicked between the surfaces. Thestructure can then be exposed to thermal activation heat and acompressing source such as a roll laminator for the bonding agentactivation and bond formation. This method provides one aspect for therealization of large scale microfluidic chip production. In alternativeaspects, the weak solvent may be applied via vapor phase or gas phasecondensation processes known in the art. Rather than cooling thesolvent, the substrate may be cooled prior to solvent application.

Another embodiment of the invention is directed to a laminated,polymeric microfluidic structure. In an aspect, the laminatedmicrofluidic structure includes a first component having first andsecond surfaces and one or more microstructures, and a second, polymericcomponent having first and second surfaces, in which the secondcomponent is fixedly attached to the first component by a weak solventbonding agent. In a particular aspect, the weak solvent bonding agent isacetonitrile. In various aspects, the second surface may be a polymericthin film that encloses the microstructures on the first component.Alternatively, the laminated structure may include a plurality (n) ofpolymeric substrate components each having one or more microstructuresthat may or may not be interconnected. The components' surfaces may beplanar and parallel, planar and non-parallel, or non-planar includingconforming curvatures or other undulations.

The foregoing and other objects, features, and advantages of embodimentsof the present invention will be apparent from the following detaileddescription of the preferred embodiments, which make reference to theseveral drawing figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A, 1B and 1C are reproduced images of a substrate componentincluding microstructures prior to and subsequent to exposure to a weaksolvent bonding agent according to an aspect of the invention;

FIG. 2 is a schematic diagram illustrating a fabrication process for alaminated, polymeric microfluidic structure according to an embodimentof the invention;

FIGS. 3A and 3B are top view reproduced images of microstructures in asubstrate component of a microfluidic structure before and after,respectively, enclosing the microstructures according to an exemplaryembodiment of the invention;

FIG. 3C is a cross-sectional view reproduced images of the structureshown in FIG. 3B;

FIG. 4 is a diagrammatic illustration of a laminated microfluidicstructure fabrication method including an alignment step according to anillustrative aspect of the invention;

FIG. 5 is a diagrammatic illustration of a laminated microfluidicstructure fabrication method for a topographically complex structureusing repetitive solvent lamination according to an illustrative aspectof the invention; and

FIGS. 6A and 6B are an exploded assembly view and a schematicperspective view, respectively, of a laminated microfluidic structureaccording to an exemplary embodiment of the invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

As used herein, the word “microstructure” generally refers to structuralfeatures on a microfluidic substrate component with walls having atleast one dimension in the range of about 0.1 micrometer to about 1000micrometers. These features may be, but are not limited to,microchannels, microfluidic pathways, microreservoirs, microvalves ormicrofilters. The term “polymeric” refers to a macromolecular structureor material having a molecular weight that is substantially higher thanthe constituent monomers and, which is produced by a polymerizationreaction. All materials commonly and herein referred to as “plastic”materials are polymeric materials. The term “acrylic” refers toAcrylite®, Plexiglas®, PMMA or other trade names ofpolymethylmethacrylate. A “two-dimensional microfluidic network” refersto fluidic connectivity of at least two microfluidic pathways orchannels that co-exist within a component or in the plane of a planarcomponent. A “three-dimensional microfluidic network” refers to fluidicconnectivity of at least three microfluidic pathways or channelsarranged in such a way that at least one of the three channels is out ofthe plane of the component or in another, non-planer component. The termof “weak solvent” as used herein refers to an organic solvent capable offorming a chemically bonded interface between two mating surfaces underappropriate temperature, force (i.e., due to pressure, vacuum and/ormass) conditions but having little or substantially no bonding effectotherwise. The term “inert solvent” refers to a solvent that is misciblewith the weak solvent but having no bonding capability alone.

Embodiments of the invention are based on the surprising discovery bythe inventors that when a weak solvent bonding agent is used as alamination solvent to join non-elastomeric polymers such as polystyrene,polycarbonate, acrylic or other linear polymers under mild conditions,microstructures disposed on the substrate are not adversely affected.This discovery enables practical and economical fabrication of prototypeas well as production fabrication of laminated, polymeric microfluidicstructures.

According to an aspect, the weak solvent bonding agent may be chemicallydefined as:

where, R1=H or R, where R=alkyl or is absent, R2=H or R, where R=alkylor is absent, and R3=H or R, where R=alkyl or is absent.

Alternatively, the weak solvent may have a chemical formula of:

where, R1=H or R, where R=alkyl or is absent and R2=H or R, whereR=alkyl or is absent.

Alternatively, the weak solvent may have a chemical formula of:

where, R1=H or R, where R=alkyl or is absent.

In a particular aspect, the weak solvent bonding agent is acetonitrile.Acetonitrile is a versatile solvent that is widely used in analyticalchemistry and other applications. It is 100% miscible with water andexhibits excellent optical properties. Acetonitrile has a favorabledielectric constant, solubility parameters and low hydrogen bondingability, which make it a useful solvent for protein and DNA sequencing.Acetonitrile, however, is not typically a solvent of choice for organicsynthesis due to its limited solubility to many organic molecules. Infact, compared to many ketones, halogenated hydrocarbons, ether oraromatic molecules, acetonitrile has very limited ability to swellpolymeric materials. As such, acetonitrile is referred to herein as aweak solvent. Since it is used as a bonding agent in the variousembodiments of the invention described in detail below, it represents anexemplary weak solvent bonding agent for laminating polymericmicrofluidic structures. Thus the weak ability of acetonitrile todissolve a plastic surface makes it highly suitable for laminatingpolymeric materials such as polystyrene, polycarbonate, acrylic andother linear polymers. For example, microstructures disposed on apolystyrene substrate that was treated with acetonitrile at roomtemperature for at least several minutes did not exhibit any noticeablefeature damage. Acrylic and polycarbonate have been observed to be moresusceptible than polystyrene to acetonitrile, but this increasedsusceptibility can be controlled by applying the acetonitrile at a lowertemperature or, alternatively, by using a combination of acetonitrileand other inert solvents.

FIG. 1 illustrates the physical stability of a polystyrene substrate andassociated microstructures that was exposed to acetonitrile. Testmicrostructures 100 ranging from about 2.5 to 5 μm in size, andapproximately 10 μm in depth were replicated on 1 mm thick polystyrenesheets 110. FIG. 1A shows an image of the test microstructures 100 priorto the acetonitrile exposure. FIG. 1B shows an image of the testmicrostructures 100 covered with the acetonitrile. FIG. 1C shows animage of the test microstructures 100 after exposure to the acetonitrileat room temperature for 5 minutes. There is no sign that acetonitriletreatment at room temperature caused any noticeable surfacedeterioration of the test microstructures.

An apparently unique feature of acetonitrile lamination is that thisweak solvent has remarkably different solubility strengths at differenttemperatures when used in relation to polymeric components ofmicrofluidic structures according to embodiments of the invention.Although it is well known that the solubility of most inorganic ororganic substances increases as the temperature of the applied solventrises, utilizing this solubility variation at different temperature forcontrolled microfluidic structure solvent lamination requires a fineoperating window. The substrate must be able to withstand solventtreatment at room temperature while increasing its solubilitysufficiently at elevated temperature and pressure. Acetonitrile used asa laminated microfluidic structure bonding agent provides the requiredoperating range in contrast to all currently known strong organicsolvents that are generally used for solvent lamination.

An embodiment of the invention is directed to a method for making alaminated, polymeric microfluidic structure. FIG. 2 illustrates anexemplary two-step acetonitrile-based weak solvent bonding agentlamination process 200 used to fabricate a polystyrene microfluidicstructure 9. An exemplary first component 1 comprising a polystyreneplaner base plate that includes 1 to n microstructures 2 is provided atstep 225. An intended contact surface 11 of the base plate 1 was wettedwith acetonitrile at step 230 a by dipping the component into a solventcontainer 3 containing acetonitrile 4 at room temperature.Alternatively, as shown at step 230 b, the acetonitrile 4 can be sprayedvia a nozzle 10 onto the intended contact surface 11 of the base plate 1at room temperature. A second component 5, shown as a cover platecontaining fluid communication through-holes 6, is provided at step 235.The cover plate was adjacently contacted with the surface 11 of thefirst component 1 at step 240. The microstructures 2 and thethrough-holes 6 can be aligned by sliding the cover plate in relation tothe base plate or vice-versa to initially form the assembly 9 shown at245. At step 250, the assembly 9 is placed atop a hot plate 8 at 40-45°C. to thermally activate the acetonitrile while being compressed by aroller 7. The bonding process was completed in about 1 minute for apolymeric sheet of 1 mm thickness to yield a finished, laminatedmicrofluidic chip structure 9 shown at 255. The bonding quality andyield may be improved upon if a temperature-controlled press or a rolllaminator is used in place of the hot plate 8 and the roller 7.

The acetonitrile-bonded, laminated microfluidic structure 9 set forth inFIG. 3 was analyzed topographically and in cross-section. Themicrostructures 2 of the structure 9 are microfluidic pathways ofbetween about 200 to 1000 μm in width and 30 μm deep. The base plate 1is a 1 mm thick polystyrene substrate in which the pathways aredisposed. The cover plate 5 is a 1 mm thick polystyrene substrate. Themicrofluidic pathways 2 were enclosed by the process described abovewith reference to FIG. 2. FIGS. 3A and 3B are top view images before andafter enclosing the microfluidic pathways 2 via lamination of the baseplate 1 and the cover plate 5, respectively. FIG. 3C is across-sectional view of the enclosed pathway. Substantially no pathwaydeformation or other dimensional alternation is observed. The integrityof the surface of the structure, and optical clarity of the substrate, 9are also retained as there is no observable cracking or other materialdamage.

A beneficial aspect of acetonitrile-bonded lamination is that theprocess according to an embodiment of the invention allows substratealignment for structures containing multi-component layers or fluidnetworks constructed utilizing both the cover plate and the base plate.Unlike conventional strong solvent lamination, which tends to penetratethe polymeric substrate surface aggressively and create a tacky bondingsurface within seconds of solvent application, acetonitrile at roomtemperature exhibits a very weak power to soften the substrate uponapplication. When the acetonitrile is present between the matedsurfaces, at lower temperature prior to thermal activation, it functionssimilar to a lubricant and allows the adjacently contacted surfaces toslide freely against each other. Upon thermal activation of theacetonitrile and application of pressure, the mated surfaces form asubstantially irreversible bond.

The alignment aspect of the process is illustrated by example in FIG. 4.At step 400 polystyrene base plate 12 containing microstructures 14 andalignment keys 15 is wetted with acetonitrile at room temperature in asuitable manner, such as described above. A cover plate 13 of the samematerial, containing fluid loading ports 16 and alignment keys 17 isplaced atop the base plate 12 in adjacent contact at step 410. Thestacked assembly 18 is aligned at step 420 using the alignment keys 15and 17 to give the aligned assembly 19. The aligned assembly 19 is thenlaminated at an elevated temperature and pressure for a short period, at425, resulting in the finished, laminated microfluidic structure 20.Exemplary ranges of the temperature of the applied acetonitrile arebetween about minus 10 to positive 35° C., more particularly betweenabout 0 to +20° C. The thermal activating temperature is above about+35° C. Exemplary amounts of pressure applied to the adjacentlycontacted components to assist the laminating process are up to about 10psi, more particularly between 0 to 2.5 psi. Illustrative compressiontime of the lamination process is from seconds to minutes when a rolllaminator or a heated platen press is used.

Formation of three-dimensional fluid networks is critical for developingmicrofluidic applications. Similar to the two-dimensional printedcircuit board (PCB) case in which the “printed” wires cannot cross eachother without electric connectivity, fluidic channels or pathways alsocannot cross each other without fluidic connectivity. To build a simplecrossover structure in a microfluidic chip, the fluid channels must belocated at different layers at the crossover section and be joined byvertical fluid pathways to complete the fluid network.

FIG. 5 illustrates an embodiment of the invention directed to thefabrication process for the formation of a three-dimensional fluidnetwork microfluidic structure. The illustrated process utilizes athree-layer substrate, two-step weak solvent bonding lamination process.A first, polymeric base plate component 21 is provided that includesmicrostructures 25 and alignment keys 23, which are produced, forexample, by direct machining, hot embossing or micromolding. A second,polymeric cover plate component 22 having fluid through-holes 26 andalignment keys 24 is also provided. At step 1000, an appropriate surface38 of the first component 21 is wetted with weak solvent bonding agentacetonitrile at room temperature. The second component 22 is set atopthe base plate 21 such that top surface 38 of component 21 and opposingbottom surface 42 of component 22 are in adjacent contact. The stackedcomponents 21 and 22 are slidingly aligned aided by the alignment keys23 and 24. The structure is then laminated/bonded at elevatedtemperature and pressure (in the ranges described herein above) at step1010 to produce the lower level microfluidic assembly 28. A third, coverplate component 29, including a partial fluid network 31, through-holes30 and alignment keys 32, is provided at step 1015. A top surface 43 ofassembly 28 is wetted with weak solvent bonding agent acetonitrile atroom temperature as described previously. The third component 29 is thenset atop the assembly 28 such that top surface 43 of component 22 andopposing bottom surface 44 of component 29 are in adjacent contact. Thestacked components 28 and 29 are slidingly aligned with the aid ofalignment keys 24, 32. The structure is then laminated/bonded atelevated temperature and pressure (in the ranges described herein above)at step 1020 to produce the three-dimensional microfluidic structure 33,which includes two crossover microstructures 34 and 35. While bothcrossover microstructures 34, 35 deliver fluids across each otherwithout fluidic connectivity, the fluidic patterns generated by thesetwo crossover microstructures on the base plate 21 are distinctlydifferent. The crossover microstructure 35 is formed by enclosing twostraight channels 36 and 37, which are fabricated at different levels ofthe microfluidic structure 33. No common plane is shared by differentchannels or channel segments. The other crossover microstructure 34 isconsiderably more complicated. In addition to providing a non-conductivefluidic crossover pathway, crossover microstructure 34 also enables asegment of the upper fluid network 51 to coexist on the same plane 38and leads to the formation of an isolated fluid segment 51 intwo-dimensional space as shown in component 21. The utility of adiscontinuous fluid segment in two-dimensional space is described inU.S. Patent Application No. 20030156992, entitled Microfluidic systemsincluding three-dimensionally arrayed channel networks, incorporatedherein by reference in its entirety to the fullest allowable extent.FIGS. 6A and 6B illustrate exploded and assembled views, respectively,of the microfluidic structure resulting from the fabrication processdescribed in association with FIG. 5.

In the case where the microstructure(s) in a component is small, e.g.,having a depth on the order of about 5 μm or less, and the planar widthof the pattern is large, e.g., 1 mm or more, and in addition theenclosing component is a thin film having a thickness of about 200 μm orless, the lamination force applied to the component pair may cause theupper component to impinge upon and bond to the lower component causingblockage of the pathway. One way to prevent this problem is to controlthe presence of bonding agent in the microstructure(s). If the appliedbonding agent is not present in the pathway during thermal activation,the upper component will not bond to the pathway of the lower component.The upper component will lift back to its intended position when theassembly returns to room temperature.

There are a number of ways in which the acetonitrile bonding agent canbe manipulated to allow lamination of two components without deformingthe enclosed microstructure(s). When the base component containing themicrostructure(s) is brought into contact with the cover component, thespace between the two components may typically be on the order of about50 to 100 nm, which is much less than the depth of the microstructures,i.e., about 1 μm or more. It is well known that the capillary force of aliquid is indirectly proportional to the width of the gap the liquid isfilling. Thus there will be a higher capillary force in the area to bebonded than in the microstructure(s). This phenomena can be exploited tocontain the weak solvent only to the areas of the structure intended forbonding. As previously mentioned, the two substrates can be sprayed withsolvent and then contacted. The solvent will generally completely fillthe void between the substrates, including the microstructures. Thesolvent can subsequently be suctioned from the microstructures leavingthe solvent to remain only in the areas between the substrates that areintended for bonding to occur. Alternatively, if the opposing surfacesof the substrates are put in adjacent contacted prior to solventexposure, the solvent can then be introduced to the exposed edge of thecontacted components. The solvent will “wick” into the area where thecomponents are in contact while the microstructures remain solvent-free.

As disclosed above, the acetonitrile bonding agent requires thermalactivation in order to create a bond between the polymeric components.The requisite heating can be provided in a number of ways. When the heatis applied to the components by positioning them on a heat source, theheat must be conducted through the components to the bonding interface.This method, while simple, may not be amenable for applications wherethe substrate is bulky or there are fine structures sensitive to thesolvent treatment under thermally activated conditions. Another methodaspect that provides the necessary energy at the bonding interfacewithout significantly heating the substrate components is referred toherein as solvent-assisted microwave bonding. In this method thesubstrate components are prepared for bonding as previously disclosed.However, instead of conventional heating the bulk structure bycontacting a high temperature source, the assembled component pair isexposed to microwave energy. The microwaves energy is predominatelyabsorbed by the polar solvent molecules without affecting the bulkplastic component structure, thus heating the bonding interface withoutbulk heating of the substrates. This method is particularly useful insituations where the heating area needs to be surface restricted.Alternatively, the structure to be bonded or laminated by the weaksolvent bonding agent may be cooled prior to weak solvent application.

The foregoing description of the preferred embodiment of the inventionhas been presented for the purposes of illustration and description. Itis not intended to be exhaustive or to limit the invention to theprecise form disclosed. Many modifications and variations are possiblein light of the above teaching. It is intended that the scope of theinvention be limited not by this detailed description but rather by theclaims appended hereto.

1. A method for laminating at least two polymeric components to form alaminated, polymeric microfluidic structure, comprising: applying a weaksolvent to a surface of one of the at least two components at a firsttemperature; adjacently contacting opposing surfaces, including thesurface having the applied weak solvent, of the at least two components;and creating a thermal activation condition by raising the temperatureto a second temperature that is greater than the first temperature forthermally activating the weak solvent, wherein the weak solvent has achemical formula of:

where, R1=H or R, where R=alkyl or is absent, R2=H or R, where R=alkylor is absent, and R3=H or R, where R=alkyl or is absent.
 2. A method forlaminating at least two polymeric components to form a laminated,polymeric microfluidic structure, comprising: applying a weak solvent toa surface of one of the at least two components at a first temperature;adjacently contacting opposing surfaces including the surface having theapplied weak solvent, of the at least two components; and creating athermal activation condition by raising the temperature to a secondtemperature that is greater than the first temperature for thermallyactivating the weak solvent, wherein the weak solvent has a chemicalformula of:

where, R1=H or R, where R=alkyl or is absent, and R2=H or R, whereR=alkyl or is absent.
 3. A method for laminating at least two polymericcomponents to form a laminated, polymeric microfluidic structure,comprising: applying a weak solvent to a surface of one of the at leasttwo components at a first temperature; adjacently contacting opposingsurfaces, including the surface having the applied weak solvent, of theat least two components; and creating a thermal activation condition byraising the temperature to a second temperature that is greater than thefirst temperature for thermally activating the weak solvent, wherein theweak solvent has a chemical formula of:

where, R1=H or R, where R=alkyl or is absent.
 4. A method for laminatingat least two polymeric components to form a laminated, polymericmicrofluidic structure, comprising: applying a weak solvent to a surfaceof one of the at least two components at a first temperature; adjacentlycontacting opposing surfaces, including the surface having the appliedweak solvent, of the at least two components; and creating a thermalactivation condition by raising the temperature to a second temperaturethat is greater than the first temperature for thermally activating theweak solvent, wherein the weak solvent is acetonitrile.
 5. A method ofmaking a laminated, polymeric microfluidic structure, comprising:providing a first component having first and second surfaces, wherein atleast one of the surfaces includes a micro structure, further whereinthe first component is a polymeric material; providing at least asecond, polymeric component having first and second surfaces, whereinone of the first and second surface of the first component is intendedto be fixedly attached to a respective second and first opposing surfaceof the second component; applying a weak solvent bonding agent withrespect to the polymeric components to at least one of the first and thesecond component at a first temperature; creating a thermal activationcondition b raisin the temperature to a second temperature that isgreater than the first temperature for thermally activating the weaksolvent; and adjacently contacting the opposing surface, wherein theweak solvent bonding agent is acetonitrile.
 6. The method of claim 5,wherein applying the weak solvent bonding agent comprises spraying thebonding agent onto one of the first and second surface of at least oneof the first and second component.
 7. The method of claim 5, whereinapplying the weak solvent bonding agent comprises dipping at least oneof the first and second component into a supply of the bonding agent. 8.The method of claim 5, wherein applying the bonding agent comprisesadjacently contacting the first and second components and applying theweak solvent bonding agent to at least one common edge of the adjacentlycontacted components.
 9. The method of claim 5, further comprisingaligning the first and second components after adjacently contactingthem, after applying the bonding agent, prior to thermally activatingthe applied bonding agent.
 10. The method of claim 5, further comprisingaligning the first and second components after adjacently contactingthem, before applying the bonding agent.
 11. The method of claim 5,further comprising applying pressure to the exposed surfaces of theadjacently connected components during the thermal activation of thebonding agent.
 12. The method of claim 5, wherein the step of applying aweak solvent bonding agent further comprises controlling the presence ofthe bonding agent in the microstructure.
 13. The method of claim 12,wherein controlling the presence of the bonding agent in themicrostructure comprises physically separating at least a portion of themicrostructure from the second component.
 14. The method of claim 5,comprising thermally activating the applied bonding agent afteradjacently contacting the opposing surfaces.
 15. The method of claim 5,comprising applying the weak solvent bonding agent at approximately roomtemperature or lower.
 16. The method of claim 1, comprising cooling theone of the at least two components prior to applying the weak solvent.17. The method of claim 1, comprising thermally activating the appliedweak solvent after adjacently contacting opposing surfaces of the atleast two components.
 18. The method of claim 1, further comprisingapplying pressure to the at least two components after applying the weaksolvent.
 19. The method of claim 17, further comprising aligning the atleast two components prior to thermally activating the applied weaksolvent.
 20. The method of claim 1, further comprising sliding the atleast two components into a desired alignment after applying the weaksolvent and adjacently contacting opposing surfaces of the at least twocomponents.
 21. The method of claim 1, further comprising aligning theat least two components into a desired alignment prior to applying theweak solvent and after adjacently contacting opposing surfaces of the atleast two components.
 22. The method of claim 2, comprising cooling theone of the at least two components prior to applying the weak solvent.23. The method of claim 2, comprising thermally activating the appliedweak solvent after adjacently contacting opposing surfaces of the atleast two components.
 24. The method of claim 2, further comprisingapplying pressure to the at least two components after applying the weaksolvent.
 25. The method of claim 23, further comprising aligning the atleast two components prior to thermally activating the applied weaksolvent.
 26. The method of claim 2, further comprising sliding the atleast two components into a desired alignment after applying the weaksolvent and adjacently contacting opposing surfaces of the at least twocomponents.
 27. The method of claim 2, further comprising aligning theat least two components into a desired alignment prior to applying theweak solvent and after adjacently contacting opposing surfaces of the atleast two components.
 28. The method of claim 3, comprising cooling theone of the at least two components prior to applying the weak solvent.29. The method of claim 3, comprising thermally activating the appliedweak solvent after adjacently contacting opposing surfaces of the atleast two components.
 30. The method of claim 3, further comprisingapplying pressure to the at least two components after applying the weaksolvent.
 31. The method of claim 29, further comprising aligning the atleast two components prior to thermally activating the applied weaksolvent.
 32. The method of claim 3, further comprising sliding the atleast two components into a desired alignment after applying the weaksolvent and adjacently contacting opposing surfaces of the at least twocomponents.
 33. The method of claim 3, further comprising aligning theat least two components into a desired alignment prior to applying theweak solvent and after adjacently contacting opposing surfaces of the atleast two components.
 34. The method of claim 4, comprising cooling theone of the at least two components prior to applying the weak solvent.35. The method of claim 4, comprising thermally activating the appliedweak solvent after adjacently contacting opposing surfaces of the atleast two components.
 36. The method of claim 4, further comprisingapplying pressure to the at least two components after applying the weaksolvent.
 37. The method of claim 35, further comprising aligning the atleast two components prior to thermally activating the applied weaksolvent.
 38. The method of claim 4, further comprising sliding the atleast two components into a desired alignment after applying the weaksolvent and adjacently contacting opposing surfaces of the at least twocomponents.
 39. The method of claim 4, further comprising aligning theat least two components into a desired alignment prior to applying theweak solvent and after adjacently contacting opposing surfaces of the atleast two components.